Estrogen receptor-related receptor-alpha (ERR-alpha) is dysregulated in inflammatory arthritis.
OBJECTIVE
Subchondral bone loss is a characteristic feature of inflammatory arthritis. Recently, estrogen receptor-related receptor-alpha (ERR-alpha), an orphan nuclear receptor, has been found to be involved in activation of macrophages. We hypothesized that ERR-alpha which is expressed and also functional in articular chondrocytes, osteoblasts and osteoclasts, may be involved in rodent models of inflammatory arthritis.


METHODS
Erosive arthritis was induced in DBA/1 mice by injection of type II collagen in Freund's complete adjuvant. RNA was isolated from the bone and joints and expression of ERR-alpha and cartilage (GDF5 and Col2a1) and bone [bone sialoprotein (BSP) and osteocalcin (OCN)] markers was analysed by semi-quantitative PCR.


RESULTS
We report for the first time that the expression of ERR-alpha is dysregulated in bones and joints in a mouse model of inflammatory arthritis. Specifically, we show that ERR-alpha expression is down-regulated early in bone and later in joints of mice with type II CIA. Concomitantly, temporal changes were observed in GDF-5 and Col2a1 expression in joints following both initial injection and booster injection of type II collagen. Similarly, down-regulation of ERR-alpha mRNA expression in subchondral bone in mice with induced joint inflammation was also paralleled by down-regulation of markers of bone formation (BSP, OCN).


CONCLUSIONS
These data suggest that dysregulation of ERR-alpha expression may precede and contribute to the destruction of cartilage and bone accompanying inflammatory arthritis.
Bonnelye
E
E
Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Room 6233, Medical Sciences Building, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Laurin
N
N
Jurdic
P
P
Hart
D A
DA
Aubin
J E
JE
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression; D007596:Joints / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000097983:ERRalpha Estrogen-Related Receptor
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor